Enhanced cognitive activity-over and above social or physical activity-is required to protect Alzheimer's mice against cognitive impairment, reduce Aβ deposition, and increase synaptic immunoreactivity
Enhanced cognitive activity-over and above social or physical activity-is required to protect Alzheimer's mice against cognitive impairment, reduce Aβ deposition, and increase synaptic immunoreactivity
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DOI：
10.1016/j.nlm.2007.07.007
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发表时间：
2007-10-01
影响因子：
2.7
通讯作者：
Arendash, Gary W.
中科院分区：
文献类型：
--
作者：
Cracchiolo, Jennifer R.;Mori, Takashi;Arendash, Gary W.
虽然社会、身体和认知活动都被认为可以降低阿尔茨海默病（AD）的风险，但流行病学研究无法确定哪种活动或活动组合最重要。为了解决这个问题，从1 1/2月龄到9个月大，在四种住房条件（贫困、社会、社会+身体或完全富裕）中长期饲养突变型APP转基因AD小鼠。因此，社会、身体和增强的认知活动逐步分层。在最后5周的住宿期间，进行了一整套感觉运动、焦虑和认知任务的行为评估。只有完全富集（即认知活动增强）的AD小鼠表现出：(1)对认知障碍的保护，(2)脑p -淀粉样蛋白沉积减少，(3)海马突触免疫反应性增加。增强的认知活动提供的保护跨越多个认知领域（工作记忆、参考学习和识别/识别）。完全富集的认知和神经组织学益处在血液细胞因子或皮质酮水平没有任何变化的情况下发生，这表明富集依赖机制分别不涉及炎症反应或应激水平的变化。这些结果表明，阿尔茨海默病小鼠的认知和神经益处需要完全富集的认知活动增强-身体和/或社交活动不足。因此，我们的数据表明，强调终生高水平认知活动（超过社会和身体活动）的人将获得最大的环境保护，以防止AD。(c) 2007爱思唯尔公司版权所有。
Although social, physical, and cognitive activities have each been suggested to reduce the risk of Alzheimer's disease (AD), epidemiologic studies cannot determine which activity or combination of activities is most important. To address this question, mutant APP transgenic AD mice were reared long-term in one of four housing conditions (impoverished, social, social + physical, or complete enrichment) from 1 1/2 through 9 months of age. Thus, a stepwise layering of social, physical, and enhanced cognitive activity was created. Behavioral evaluation in a full battery of sensorimotor, anxiety, and cognitive tasks was carried out during the final 5 weeks of housing. Only AD mice raised in complete enrichment (i.e., enhanced cognitive activity) showed: (1) protection against cognitive impairment, (2) decreased brain P-amyloid deposition, and (3) increased hippocampal synaptic immunoreactivity. The protection provided by enhanced cognitive activity spanned multiple cognitive domains (working memory, reference learning, and recognition/identification). Cognitive and neurohistologic benefits of complete enrichment occurred without any changes in blood cytokine or corticosterone levels, suggesting that enrichment-dependent mechanisms do not involve changes in the inflammatory response or stress levels, respectively. These results indicate that the enhanced cognitive activity of complete enrichment is required for cognitive and neurologic benefit to AD mice-physical and/or social activity are insufficient. Thus, our data suggest that humans who emphasize a high lifelong level of cognitive activity (over and above social and physical activities) will attain the maximal environmental protection against AD. (c) 2007 Elsevier Inc. All rights reserved.